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Membrane-mediated Anesthesia
Membrane-mediated anesthesia or anaesthesia (UK) is a mechanism of action that involves an anesthetic exerting its effects through the lipid membrane. Established mechanism exists for both general and local anesthetics. The anesthetic binding site is within ordered lipids and binding disrupts the function of the ordered lipid. The contribution of membrane-mediated anesthesia, relative to other mechanisms, is not yet clear. See Theories of general anaesthetic action for a broader discussion of purely theoretical mechanisms. General anesthetics Inhaled anesthetics partition into the membrane and disrupt the function of ordered lipids. Membranes, like proteins are composed of ordered and disordered regions. The ordered region of the membrane contain a palmitate binding site that drives the association of palmitoylated proteins to clusters of GM1 lipids (sometimes referred to as lipid rafts). Palmitate's binding to lipid rafts regulates the affinity of most proteins to lipid rafts. Inha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mechanism Of Action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives. In contrast, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance. Importance Elucidating the mechanism of action of novel drugs and medications is important for several reasons: * In the case of anti-infe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Theories Of General Anaesthetic Action
A general anaesthetic (or anesthetic) is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist/anesthesiologist in order to induce or maintain general anaesthesia to facilitate surgery. General anaesthetics have been widely used in surgery since 1842 when Crawford Long for the first time administered diethyl ether to a patient and performed a painless operation. It has long been believed that general anaesthetics exert their effects (analgesia, unconsciousness, immobility) through a membrane mediated mechanism or by directly modulating the activity of membrane proteins in the neuronal membrane. In general, different anaesthetics exhibit different mechanisms of action such that there are numerous molecular targets at all levels of integration within the central nervous system. However, for certain intravenous anaesthetics, such as propofol and etomidate, the main molecular target has been identified to be GABAA rec ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inhaled Anesthetics
An inhalational anesthetic is a chemical compound possessing general anesthetic properties that can be delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon. List of inhalational anaesthetic agents Currently-used agents * Desflurane * Isoflurane * Nitrous oxide * Sevoflurane * Xenon Previously-used agents Although some of these are still used in clinical practice and in research, the following anaesthetic agents are primarily of historical interest in developed countries: * Acetylene * Chloroethane (ethyl chloride) * Chloroform * Cryofluorane * Cyclopropane * Diethyl ether * Divinyl ether * Enflurane * Ethylene * Fluroxene * Halothane (still wid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Palmitate
Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The Lipid Handbook, 3rd ed. Boca Raton: CRC Press, 2007. , Its chemical formula is CH3(CH2)14COOH, and its C:D (the total number of carbon atoms to the number of carbon-carbon double-bonds) is 16:0. It is a major component of the oil from the fruit of oil palms (palm oil), making up to 44% of total fats. Meats, cheeses, butter, and other dairy products also contain palmitic acid, amounting to 50–60% of total fats. Palmitates are the salts and esters of palmitic acid. The palmitate anion is the observed form of palmitic acid at physiologic pH (7.4). Occurrence and production Palmitic acid was discovered by Edmond Frémy in 1840, in saponified palm oil. This remains the primary industrial route for its production, with the triglycerides (fa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Palmitoylated
Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typically membrane proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins between membrane compartments, as well as in modulating protein–protein interactions. In contrast to prenylation and myristoylation, palmitoylation is usually reversible (because the bond between palmitic acid and protein is often a thioester bond). The reverse reaction in mammalian cells is catalyzed by acyl-protein thioesterases (APTs) in the cytosol and palmitoyl protein thioesterases in lysosomes. Because palmitoylation is a dynamic, post-translati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Substrate Presentation
Substrate presentation is a biological process that activates a protein. The protein is sequestered away from its substrate and then activated by release and exposure of the protein to its substrate. A substrate is typically the substance on which an enzyme acts but can also be a protein surface to which a ligand binds. The substrate is the material acted upon. In the case of an interaction with an enzyme, the protein or organic substrate typically changes chemical form. Substrate presentation differs from allosteric regulation in that the enzyme need not change its conformation to begin catalysis. Substrate presentation is best described for nanoscopic distances (<100 nm). 
Examples Amyloid Precursor Protein [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PIP2 Domain
PIP2 domains (also called PIP2 clusters) are a type of cholesterol-independent lipid domain formed from phosphatidylinositol and positively charged proteins in the plasma membrane. They tend to inhibit GM1 lipid raft function. Chemical properties Phosphatidylinositol 4,5-bisphosphate (PIP2) is a anionic signaling lipid. Its polyunsaturated acyl chains exclude it from GM1 lipid rafts. The multiple negative charges on PIP2 are thought to cluster proteins with positive charges residing in the plasma membrane leading to nanoscale clusters. PIP3 is also clustered away from PIP2 and away from GM1 lipid rafts. Biological function PIP2 domains inhibit GM1 domain function by attracting palmitoylated proteins away from GM1 lipid rafts. For this to occur a protein must be both palmitoylated and bind PIP2. Presumably PIP2 could also antagonize PIP3 localization but this has not been shown directly. PLD2 Phospholipase D2 (PLD2) binds PIP2 and localizes with lipid rafts. Increases in choles ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TREK-1
Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the ''KCNK2'' gene. This gene encodes K2P2.1, a lipid-gated ion channel belonging to the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that releases potassium out of the cell to control resting membrane potential. The channel is opened by anionic lipid, certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene. Function in neurons TREK-1 is part of the subfamily of mechano-gated potassium channels that are present in mammalian neurons. They can be gated in both chemical and physical ways and can be opened via both physical stimuli and chemical stimuli. TREK-1 channels are found in a variety of tissues, but are particularly abundant in the brain and heart and are seen in various t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidic Acid
Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty acids. They constitute about 0.25% of phospholipids in the bilayer. Structure Phosphatidic acid consists of a glycerol backbone, with, in general, a saturated fatty acid bonded to carbon-1, an unsaturated fatty acid bonded to carbon-2, and a phosphate group bonded to carbon-3. Formation and degradation Besides de novo synthesis, PA can be formed in three ways: * By phospholipase D (PLD), via the hydrolysis of the P-O bond of phosphatidylcholine (PC) to produce PA and choline. * By the phosphorylation of diacylglycerol (DAG) by DAG kinase (DAGK). * By the acylation of lysophosphatidic acid by lysoPA-acyltransferase (LPAAT); this is the most common pathway.Devlin, T. M. 2004. ''Bioquímica'', 4ª edición. Reverté, Barcelona. The glycer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
